The proposed research addresses itself to cell death in limb morphogenesis. The specific systems chosen are the zones of necrosis which occur during the normal cell development of the chick limb. We have demonstrated that if normal cell death fails to occur in the interdigits this is associated with abnormal development. The emphasis of this research is on the developmental events which occur before the cells in these zones show morphological evidence that they are dying. Microsurigical, autoradiographic, fine structure and tissue culture methods will be combined with experimental conditions which prevent death, such as introduction of metabolic inhibitors or specific tissue interactions, to study cells which normally have death as an endpoint in their immediate future. The question we are raising is: what are the factors which occur in the cells which are to die and do not occur in other cells? This includes macromolecular and morphological events which presage death, and intrinsic and extrinsic factors which affect whether cells that normally die will actually do so. BIBLIOGRAPHIC REFERENCES: Pollak, R.D. and Fallon, J.F. 1976 Autoradiographic analysis of macromolecular syntheses in prospectively necrotic cells of the chick wing bud. II. Nucleic acids. In Press. Experimental Cell Research.